PROTECTIVE ROLE OF ROSMARINUS OFFICINALIS CALLUS EXTRACT AGAINST PARACETAMOL-INDUCED OXIDATIVE DAMAGE AND MITOCHONDRIAL DYSFUNCTION IN HEPG2 CELL LINE

Ahmed R Albuhaydar

doi:10.70604/jmtbas.v3i2.194

Authors

Ahmed R. Albuhaydar College of Pharmacy, University of Al-Qadisiyah, Iraq

Abstract

Paracetamol (acetaminophen, APAP) is one of the most popular analgesic and antipyretic medications in the world, although overdose is still a major cause of acute liver failure in developed countries. The hepatotoxic process involves essentially excessive synthesis of N-acetyl-p-benzoquinone imine (NAPQI), which depletes hepatic glutathione reserves, covalently alters mitochondrial proteins, and initiates a cascade of oxidative damage leading to cell death. The current work studied the hepatoprotective effect of methanolic extract produced from Rosmarinus officinalis L. callus culture against APAP-induced cytotoxicity in human hepatocellular carcinoma (HepG2) cells. Callus cultures were produced on Murashige and Skoog medium with 2,4-dichlorophenoxyacetic acid (2,4-D) and 6-benzylaminopurine (BAP). Lyophilised callus was extracted with methanol and phytochemical screening indicated the presence of phenolic acids, flavonoids and diterpene substances such as rosmarinic acid and carnosic acid. The HepG2 cells were pre-incubated with the callus extract at various concentrations (25-200 µg/mL) before the APAP insult (10 mM, 24 h). The extract dramatically improved cell survival (from 41.8% to 84.1%), reduced the production of reactive oxygen species (ROS), restored the mitochondrial membrane potential (ΔΨm) and boosted the intracellular glutathione level in a concentration-dependent manner. Moreover, the extract lowered the level of malondialdehyde (MDA) and increased the activity of superoxide dismutase (SOD) and catalase (CAT). These findings indicate that R. officinalis callus extract offers meaningful cytoprotection against APAP-mediated hepatic injury through mitigation of oxidative stress and preservation of mitochondrial integrity.

Keywords:

Rosmarinus officinalis, callus extract, paracetamol, hepatoprotection, oxidative stress, mitochondrial dysfunction, HepG2, rosmarinic acid

DOI

https://doi.org/10.70604/jmtbas.v3i2.194

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